The Neuropathology Core will continue to play a vital role in the Mount Sinai/Bronx VA Medical Center Alzheimer's Disease Research Center (ADRC). The Neuropathology Core serves to obtain autopsy-derived brain specimens from cases of Alzheimer's disease (AD) who have been evaluated and followed longitudinally by the Clinical Core as well as AD patients identified in the Jewish Home and Hospital for the Aged, a very large academically affiliated nursing home. We strive to obtain the brain specimens will the shortest post-mortem interval and for the entire ADRC specimen collection 39% are obtained within 4 hours and 69% within 6 hours. The specimens are dissected and preserved in a manner that maximizes their utility for the needs of both the proposed experiments within the ADRC as well as other anticipated research projects. This includes snap freezing one half of the brain specimen and fixing the other half is freshly prepared paraformaldehyde. A new addition to the dissection protocol are approaches that allow for the preparation of selected regions of the brain in such a way that the non-biased sampling techniques for stereology can be applied to quantify lesions and neuron numbers. A detailed neuropathology workup is carried out to establish a neuropathologic diagnosis as well as to document the extent and distribution of relevant neuropathologic lesions. These data are entered into an extensive data base which can be integrated into the clinical data base for the purpose cliniconeuropathologic correlative investigations. The Neuropathology Core will also provide assistance and expertise in the morphologic evaluation of newly developed transgenic animals and interpret the nature of any identified lesions for their relevance as models of AD or other human neurodegenerative conditions. Because the ADRC Brain Bank has been operating for approximately 13 years, an efficient and effective operating structure for the Brain Bank already exists. The tissues we have collected have been extensively used in a wide range of studies. They are extensively requested both by researchers within the ADRC, the greater Mount Sinai research community and by many other investigators through the US and even internationally. The overall aim of this core is to continue to maintain and operate the Brain Bank in such a way as to meet the needs of the cores and studies in the ADRC in an optimal fashion.